19-Hydroxy-19-methyl-PG amides

ABSTRACT

The present invention provides novel 19-hydroxy-19-methyl-PG amides and methods for their preparation and pharmacological uses for the induction of prostaglandin-like effects.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a division of Ser. No. 025,878, filed Apr. 2, 1979, now abandoned.

BACKGROUND OF THE INVENTION

The present invention relates to novel prostaglandin analogs. Particularly, these compounds are analogs of the prostaglandins wherein the C-19 position is substituted by hydroxy, i.e., 19-hydroxy-19-methyl-PG compounds. Most particularly, the present invention relates to novel 19-hydroxy-19-methyl-PG amides, a disclosure of the preparation and use of which is incorporated here by reference from U.S. Pat. No. 4,228,104.

PRIOR ART

Prostaglandin analogs exhibiting hydroxylation in the 19-position are known in the art. See, for example, U.S. Pat. No. 4,127,612, Sih, J. C., Prostaglandins 13:831 (1977) and U.S. Pat. Nos. 3,657,316, 3,878,046, and 3,922,297. See also the additional references cited in U.S. Ser. No. 025,878, now abandoned.

SUMMARY OF THE INVENTION

The present invention particularly provides a compound of the formula ##STR1## wherein D is (1) cis--CH═CH--CH₂ --(CH₂)_(g) --CH₂ --,

(2) cis--CH═CH--CH₂ --(CH₂)_(g) --CF₂ --,

(3) cis--CH₂ --CH═CH--CH₂ --CH₂ --,

(4) trans--(CH₂)₃ --CH═CH--,

(5) --(CH₂)₃ --(CH₂)_(g) --CH₂ --,

(6) --(CH₂)₃ --CH₂ --CF₂ --,

(7) --(CH₂)₃ --O--CH₂ --,

(8) --(CH₂)₂ --O--(CH₂)₂,

(9) --CH₂ --O--(CH₂)₃ --,

(10) --(m--Ph)--(CH₂)₂ --, or

(11) --(m--Ph)--O--CH₂ --,

wherein --(m--Ph)-- is inter-meta-phenylene, and

wherein g is zero, one, two, or three;

wherein Q is α-OH:β-R₅ or α-R₅ :β-OH, wherein R₅ is hydrogen or methyl;

wherein R₇ and R₈ are hydrogen, alkyl of one to 12 carbon atoms, inclusive, benzyl, or phenyl, being the same or different;

wherein R₂ is hydrogen, hydroxyl, or hydroxymethyl;

wherein R₃ and R₄ are hydrogen, methyl, or fluoro, being the same or different, with the proviso that one of R₃ and R₄ is fluoro only when the other is hydrogen or fluoro;

wherein W is oxo, methylene, α-OH:β-H, or α-H:β-OH; and

wherein X is cis- or trans--CH═CH--, --C.tbd.C--, or --CH₂ CH₂ --.

With regard to the divalent the substituents described above (e.g., Q) these divalent radicals are defined as α-R_(i) :β-R_(j), wherein R_(i) represents the substituent of the divalent moiety in the alpha configuration with respect to the ring and R_(j) represents the substituent of the divalent moiety in the beta configuration with respect to the plane of the ring. Accordingly, when Q is defined as α-OH:β-R₅, the hydroxy of the Q moiety is in the alpha configuration, i.e., as in the natural prostaglandin, and the R₅ substituent is in the beta configuration.

Specific embodiments of the present invention include:

19-hydroxy-19-methyl-PGF₂ α, amide,

11-deoxy-11α-hydroxymethyl-19-hydroxy-19-methyl-PGF₂ α, amide,

19-hydroxy-19-methyl-PGF₂ β, amide,

11-deoxy-11α-hydroxymethyl-19-hydroxy-19-methyl-PGF₂ β, amide,

19-hydroxy-19-methyl-PGE₂, amide,

11-deoxy-11α-hydroxymethyl-19-hydroxy-19-methyl-PGE₂, amide,

9-deoxo-9-methylene-19-hydroxy-19-methyl-PGE₂, amide

9-deoxo-9-methylene-11-deoxy-19-hydroxy-19-methyl-PGE₂, amide,

9-deoxo-9-methylene-11-deoxy-11α-hydroxymethyl-19-hydroxy-19-methyl-PGE₂, amide,

4,5-didehydro-19-hydroxy-19-methyl-PGF₁ α, amide,

4,5-didehydro-19-hydroxy-19-methyl-15(S)-15-methyl-PGF₁ α, amide,

4,5,13,14-tetradehydro-19-hydroxy-19-methyl-PGF₁ α, amide,

4,5,13,14-tetradehydro-19-hydroxy-19-methyl-16,16-difluoro-PGF₁ α, amide,

4,5,13,14-tetradehydro-19-hydroxy-19-methyl-11-deoxy-PGF₁ α, amide,

4,5,13,14-tetradehydro-19-hydroxy-19-methyl-11-deoxy-16,16-difluoro-PGF.sub.1 α, amide,

4,5-dideoxy-19-hydroxy-19-methyl-11-deoxy-11α-hydroxymethyl-PGF₁ α, amide,

4,5-dideoxy-19-hydroxy-19-methyl-11-deoxy-11α-hydroxymethyl-15(S)-15-methyl-PGF₁ α, amide,

4,5,13,14-tetradehydro-19-hydroxy-19-methyl-11-deoxy-11α-hydroxymethyl-PGF₁ α, amide,

4,5,13,14-tetradehydro-19-hydroxy-19-methyl-11-deoxy-11α-hydroxymethyl-16,16-difluoro-PGF₁ α, amide,

4,5-didehydro-19-hydroxy-19-methyl-PGF₁ β, amide,

4,5-didehydro-19-hydroxy-19-methyl-15(S)-15-methyl-PGF₁ β, amide,

4,5,13,14-tetradehydro-19-hydroxy-19-methyl-PGF₁ β, amide,

4,5,13,14-tetradehydro-19-hydroxy-19-methyl-16,16-difluoro-PGF₁ β, amide,

4,5,13,14-tetradehydro-19-hydroxy-19-methyl-11-deoxy-PGF₁ β, amide,

4,5,13,14-tetradehydro-19-hydroxy-19-methyl-19-methyl-11-deoxy-16,16-difluoro-PGF₁ β, amide,

4,5-didehydro-19-hydroxy-19-methyl-11-deoxy-11α-hydroxymethyl-PGF.sub.1 β, amide,

4,5-didehydro-19-hydroxy-19-methyl-11-deoxy-11α-hydroxymethyl-15(S)-15-methyl-PGF₁ β, amide,

4,5,13,14-tetradehydro-19-hydroxy-19-methyl-11-deoxy-11α-hydroxymethyl-PGF₁ β, amide,

4,5,13,14-tetradehydro-19-hydroxy-19-methyl-11-deoxy-11α-hydroxymethyl-16,16-difluoro-PGF₁ β, amide,

4,5-didehydro-19-hydroxy-19-methyl-PGE₁, amide,

4,5-didehydro-19-hydroxy-19-methyl-15(S)-15-methyl-PGE₁, amide,

4,5,13,14-tetradehydro-19-hydroxy-19-methyl-PGE₁, amide,

4,5,13,14-tetradehydro-19-hydroxy-19-methyl-16,16-difluoro-PGE₁, amide,

4,5,13,14-tetradehydro-19-hydroxy-19-methyl-11-deoxy-PGE₁, amide,

4,5,13,14-tetradehydro-19-hydroxy-19-methyl-1l-deoxy-16,16-difluoro-PGE.sub.1, amide,

4,5-didehydro-19-hydroxy-19-methyl-11-deoxy-11α-hydroxymethyl-PGE.sub.1, amide,

4,5-didehydro-19-hydroxy-19-methyl-11-deoxy-11α-hydroxymethyl-15(S)-15-methyl-PGE₁, amide,

4,5,13,14-tetradehydro-19-hydroxy-19-methyl-11-deoxy-11α-hydroxymethyl-PGE₁, amide,

4,5,13,14-tetradehydro-19-hydroxy-19-methyl-11-deoxy-11α-hydroxymethyl-16,16-difluoro-PGE₁, amide,

4,5-didehydro-19-hydroxy-19-methyl-9-deoxo-9-methylene-PGE₁, amide,

4,5-didehydro-19-hydroxy-19-methyl-9-deoxo-9-methylene-15(S)-15-methyl-PGE.sub.1, amide,

4,5,13,14-tetradehydro-19-hydroxy-19-methyl-9-deoxo-9-methylene-PGE₁, amide,

4,5,13,14-tetradehydro-19-hydroxy-19-methyl-9-deoxo-9-methylene-16,16-difluoro-PGE₁, amide,

4,5,13,14-tetradehydro-19-hydroxy-19-methyl-9-deoxo-9-methylene-11-deoxy-PGE₁, amide,

4,5,13,14-tetradehydro-19-hydroxy-19-methyl-9-deoxo-9-methylene-11-deoxy-16,16-difluoro-PGE₁, amide,

4,5-didehydro-19-hydroxy-19-methyl-9-deoxo-9-methylene-11-deoxy-11α-hydroxymethyl-PGE₁, amide,

4,5-didehydro-19-hydroxy-19-methyl-9-deoxo-9-methylene-11-deoxy-11α-hydroxymethyl-15(S)-15-methyl-PGE₁, amide,

4,5,13,14-tetradehydro-19-hydroxy-19-methyl-9-deoxo-9-methylene-11-deoxy-11α-hydroxymethyl-PGE₁, amide,

4,5,13,14-tetradehydro-19-hydroxy-19-methyl-9-deoxo-9-methylene-11-deoxy-11α-hydroxymethyl-16,16-difluoro-PGE₁, amide,

2,3-didehydro-19-hydroxy-19-methyl-PGF₁ α, amide,

2,3-didehydro-19-hydroxy-19-methyl-16,16-difluoro-PGF₁ α, amide,

2,3-didehydro-19-hydroxy-19-methyl-15(S)-15-methyl-PGF₁ α, amide,

2,3-didehydro-19-hydroxy-19-methyl-11-deoxy-11α-hydroxymethyl-PGF.sub.1 α, amide,

2,3-didehydro-19-hydroxy-19-methyl-11-deoxy-11α-hydroxymethyl-16,16-difluoro-PGF₁ α, amide,

2,3-didehydro-19-hydroxy-19-methyl-11-deoxy-11α-hydroxymethyl-15(S)-15-methyl-PGF₁ α, amide,

2,3-didehydro-19-hydroxy-19-methyl-PGF₁ β, amide,

2,3-didehydro-19-hydroxy-19-methyl-16,16-difluoro-PGF₁ β, amide,

2,3-didehydro-19-hydroxy-19-methyl-15(S)-15-methyl-PGF₁ β, amide,

2,3-didehydro-19-hydroxy-19-methyl-11-deoxy-11α-hydroxymethyl-PGF.sub.1 β, amide,

2,3-didehydro-19-hydroxy-19-methyl-11-deoxy-11α-hydroxymethyl-16,16-difluoro-PGF₁ β, amide,

2,3-didehydro-19-hydroxy-19-methyl-11-deoxy-11α-hydroxymethyl-15(S)-15-methyl-PGF₁ β, amide,

2,3-didehydro-19-hydroxy-19-methyl-PGE₁, amide,

2,3-didehydro-19-hydroxy-19-methyl-16,16-difluoro-PGE₁, amide,

2,3-didehydro-19-hydroxy-19-methyl-15(S)-15-methyl-PGE₁, amide,

2,3-didehydro-19-hydroxy-19-methyl-11-deoxy-11α-hydroxymethyl-PGE.sub.1, amide,

2,3-didehydro-19-hydroxy-19-methyl-11-deoxy-11α-hydroxymethyl-16,16-difluoro-PGE₁, amide,

2,3-didehydro-19-hydroxy-19-methyl-11-deoxy-11α-hydroxymethyl-15(S)-15-methyl-PGE₁, amide,

2,3-didehydro-19-hydroxy-19-methyl-9-deoxo-9-methylene-PGE₁, amide,

2,3-didehydro-19-hydroxy-19-methyl-9-deoxo-9-methylene-16,16-difluoro-PGE.sub.1, amide,

2,3-didehydro-19-hydroxy-19-methyl-9-deoxo-9-methylene-15(S)-15-methyl-PGE.sub.1, amide,

2,3-didehydro-19-hydroxy-19-methyl-9-deoxo-9-methylene-11-deoxy-11α-hydroxymethyl-PGE₁, amide,

2,3-didehydro-19-hydroxy-19-methyl-9-deoxo-9-methylene-11-deoxy-11α-hydroxymethyl-16,16-difluoro-PGE₁, amide,

2,3-didehydro-19-hydroxy-19-methyl-9-deoxo-9-methylene-11-deoxy-11α-hydroxymethyl-15(S)-15-methyl-PGE₁, amide,

19-hydroxy-19-methyl-PGF₁ α, amide,

16,16-dimethyl-19-hydroxy-19-methyl-PGF₁ α, amide,

16,16-difluoro-19-hydroxy-19-methyl-PGF₁ α, amide,

13,14-dihydro-19-hydroxy-19-methyl-PGF₁ α, amide,

11-deoxy-11α-hydroxymethyl-19-hydroxy-19-methyl-PGF₁ α, amide,

11-deoxy-11α-hydroxymethyl-16,16-dimethyl-19-hydroxy-19-methyl-PGF.sub.1 α, amide,

11-deoxy-11α-hydroxymethyl-16,16-difluoro-19-hydroxy-19-methyl-PGF.sub.1 α, amide,

11-deoxy-11α-hydroxymethyl-13,14-dihydro-19-hydroxy-19-methyl-PGF.sub.1 α, amide,

19-hydroxy-19-methyl-PGF₁ β, amide,

16,16-dimethyl-19-hydroxy-19-methyl-PGF₁ β, amide,

16,16-difluoro-19-hydroxy-19-methyl-PGF₁ β, amide,

13,14-dihydro-19-hydroxy-19-methyl-PGF₂ β, amide,

19-hydroxy-19-methyl-PGE₁, amide,

16,16-dimethyl-19-hydroxy-19-methyl-PGE₁, amide,

16,16,difluoro-19-hydroxy-19-methyl-PGE₁, amide,

13,14-dihydro-19-hydroxy-19-methyl-PGE₁, amide,

11-deoxy-11α-hydroxymethyl-19-hydroxy-19-methyl-PGE₁, amide,

11-deoxy-11α-hydroxymethyl-16,16-dimethyl-19-hydroxy-19-methyl-PGE.sub.1, amide,

11-deoxy-11α-hydroxymethyl-16,16-difluoro-19-hydroxy-19-methyl-PGE.sub.1, amide,

11-deoxy-11α-hydroxymethyl-13,14-dihydro-19-hydroxy-19-methyl-PGE.sub.1, amide,

9-deoxo-9-methylene-19-hydroxy-19-methyl-PGE₁, amide,

9-deoxo-9-methylene-16,16-dimethyl-19-hydroxy-19-methyl-PGE₁, amide,

9-deoxo-9-methylene-16,16-difluoro-19-hydroxy-19-methyl-PGE₁, amide,

9-deoxo-9-methylene-13,14-dihydro-19-hydroxy-19-methyl-PGE₁, amide,

9-deoxo-9-methylene-11-deoxy-11α-hydroxymethyl-19-hydroxy-19-methyl-PGE₁, amide,

9-deoxo-9-methylene-11-deoxy-11α-hydroxymethyl-16,16-dimethyl-19-hydroxy-19-methyl-PGE₁, amide,

9-deoxo-9-methylene-11-deoxy-11α-hydroxymethyl-16,16-difluoro-19-hydroxy-19-methyl-PGE₁, amide, and

9-deoxo-9-methylene-11-deoxy-11α-hydroxymethyl-13,14-dihydro-19-hydroxy-19-methyl-PGE₁, amide.

The compounds of the present invention are particularly useful for inducing prostaglandin-like biological effects, as is described in U.S. Ser. No. 025,878, now abandoned. Uses of compounds in accordance with the present invention include, therefore, anti-asthmatic indications. 

I claim:
 1. A compound of the formula ##STR2## wherein D is (1) cis--CH═CH--CH₂ --(CH₂)_(g) --CH₂ --,(2) cis--CH═CH--CH₂ --(CH₂)_(g) --CF₂ --, (3) cis--CH₂ --CH═CH--CH₂ --CH₂ --, (4) trans--(CH₂)₃ --CH═CH--, (5) --(CH₂)₃ --(CH₂)_(g) --CH₂ --, (6) --(CH₂)₃ --CH₂ --CF₂ --, (7) --(CH₂)₃ --O--CH₂ --, (8) --(CH₂)₂ --O--(CH₂)₂, (9) --CH₂ --O--(CH₂)₃ --, (10) --(m--Ph)--(CH₂)₂ --, or (11) --(m--Ph)--O--CH₂ --,wherein --(m--Ph)-- is inter-meta-phenylene, and wherein g is zero, one, two, or three; wherein Q is α-OH:β-R₅ or α-R₅ : β-OH, wherein R₅ is hydrogen or methyl; wherein R₇ and R₈ are hydrogen, alkyl of one to 12 carbon atoms, inclusive, benzyl, or phenyl, being the same or different; wherein R₂ is, hydroxyl, or hydroxymethyl; wherein R₃ and R₄ are hydrogen, methyl, or fluoro, being the same or different, with the proviso that one of R₃ and R₄ is fluoro only when the other is hydrogen or fluoro; wherein W is oxo, methylene, α-OH:β-H, or α-H:β-OH; and wherein X is cis- or trans--CH═CH--, --C.tbd.C--, or --CH₂ CH₂ --.
 2. A compound according to claim 1, wherein g is one or three.
 3. A compound according to claim 2, wherein D is cis--CH═CH--CH₂ --(CH₂)_(g) --CH₂ --.
 4. A compound according to claim 3, wherein W is α-OH:β-H.
 5. A compound according to claim 4, wherein R₂ is hydroxyl and X is trans--CH═CH--.
 6. 19-hydroxy-19-methyl-PGF₂ α, amide, a compound according to claim
 5. 7. A compound according to claim 4, wherein R₂ is hydroxymethyl and X is trans--CH═CH--.
 8. 11-deoxy-11α-hydroxymethyl-19-hydroxy-19-methyl-PGF₂ α, amide, a compound, according to claim
 7. 9. A compound according to claim 3, wherein W is β-OH:α-H.
 10. A compound to claim 9, wherein R₂ is hydroxyl and X is trans--CH═CH--.
 11. 19-hydroxy-19-methyl-PGF₂ β, amide, a compound according to claim
 10. 12. A compound according to claim 9, wherein R₂ is hydroxymethyl and X is trans--CH═CH--.
 13. 11-deoxy-11α-hydroxymethyl-19-hydroxy-19-methyl-PGF₂ β, amide, a compound according to claim
 12. 14. A compound according to claim 3, wherein W is oxo.
 15. A compound according to claim 14, wherein R₂ is hydroxyl and X is trans--CH═CH--.
 16. 19-hydroxy-19-methyl-PGE₂, amide, a compound according to claim
 15. 17. A compound according to claim 14, wherein R₂ is hydroxymethyl and X is trans--CH═CH--.
 18. 11-deoxy-11α-hydroxymethyl-19-hydroxy-19-methyl-PGE₂, amide, a compound according to claim
 17. 19. A compound according to claim 3, wherein W is methylene.
 20. A compound according to claim 19, wherein R₂ is hydroxyl and X is trans--CH═CH--.
 21. 9-deoxo-9-methylene-19-hydroxy-19-methyl-PGE₂, amide, a compound according to claim
 20. 22. A compound according to claim 19, wherein R₂ is hydrogen and X is trans--CH═CH--.
 23. 9-deoxo-9-methylene-11-deoxy-19-hydroxy-19-methyl-PGE₂, amide, a compound according to claim
 22. 24. A compound according to claim 19, wherein R₂ is hydroxymethyl and X is trans--CH═CH--.
 25. 9-deoxo-9-methylene-11-deoxy-11α-hydroxymethyl-19-hydroxy-19-methyl-PGE₂, amide, a compound according to claim
 24. 26. A compound according to claim 2, wherein D is cis--CH₂ --CH═CH--CH₂ --CH₂ --.
 27. A compound according to claim 26, wherein W is α-OH:β-H.
 28. A compound according to claim 27, wherein R₂ is hydroxyl.
 29. A compound according to claim 28, wherein X is trans--CH═CH--.
 30. 4,5-didehydro-19-hydroxy-19-methyl-PGF₁ α, amide, a compound according to claim
 29. 31. 4,5-didehydro-19-hydroxy-19-methyl-15(S)-15-methyl-PGF₁ α, amide, a compound according to claim
 29. 32. A compound according to claim 28, wherein X is --C.tbd.C--.
 33. 4,5,13,14-tetradehydro-19-hydroxy-19-methyl-PGF₁ α, amide, a compound according to claim
 32. 34. 4,5,13,14-tetradehydro-19-hydroxy-19-methyl-16,16-difluoro-PGF₁ α, amide, a compound according to claim
 32. 35. A compound according to claim 27, wherein R₂ is hydroxymethyl.
 36. A compound according to claim 35, wherein X is trans--CH═CH--.
 37. 4,5-dideoxy-19-hydroxy-19-methyl-11-deoxy-11α-hydroxymethyl-PGF₁ α, amide, a compound according to claim
 36. 38. 4,5-dideoxy-19-hydroxy-19-methyl-11-deoxy-11α-hydroxymethyl-15(S)-15-methyl-PGF₁ α, amide, a compound according to claim
 36. 39. A compound according to claim 35, wherein X is --C.tbd.C--.
 40. 4,5,13,14-tetradehydro-19-hydroxy-19-methyl-11-deoxy-11.alpha.-hydroxymethyl-PGF₁ α, amide, a compound according to claim
 39. 41.4,5,13,14-tetradehydro-19-hydroxy-19-methyl-11-deoxy-11α-hydroxymethyl-16,16-difluoro-PGF₁ α, amide, a compound according to claim
 39. 42. A compound according to claim 26, wherein W is β-OH:α-H.
 43. A compound according to claim 42, wherein R₂ is hydroxyl.
 44. A compound according to claim 43, wherein X is trans--CH═CH--.
 45. 4,5-didehydro-19-hydroxy-19-methyl-PGF₁ β, amide, a compound according to claim
 44. 46. 4,5-didehydro-19-hydroxy-19-methyl-15(S)-15-methyl-PGF₁ β, amide, a compound according to claim
 44. 47. A compound according to claim 43, wherein X is --C.tbd.C--.
 48. 4,5,13,14-tetradehydro-19-hydroxy-19-methyl-PGF₁ β, amide, a compound according to claim
 47. 49. 4,5,13,14-tetradehydro-19-hydroxy-19-methyl-16,16-difluoro-PGF₁ β, amide, a compound according to claim
 47. 50. A compound according to claim 42, wherein R₂ is hydroxymethyl.
 51. A compound according to claim 50, wherein X is trans--CH═CH--.
 52. 4,5-didehydro-19-hydroxy-19-methyl-11-deoxy-11α-hydroxymethyl-PGF₁ β, amide, a compound according to claim
 51. 53. 4,5-didehydro-19-hydroxy-19-methyl-11-deoxy-11α-hydroxymethyl-15(S)-15-methyl-PGF₁ β, amide, a compound according to claim
 51. 54. A compound according to claim 50, wherein X is --C.tbd.C--.
 55. 4,5,13,14-tetradehydro-19-hydroxy-19-methyl-11-deoxy-11.alpha.-hydroxymethyl-PGF₁ β, amide, a compound according to claim
 54. 56. 4,5,13,14-tetradehydro-19-hydroxy-19-methyl-11-deoxy-11α-hydroxymethyl-16,16-difluoro-PGF₁ β, amide, a compound according to claim
 54. 57. A compound according to claim 26, wherein W is oxo.
 58. A compound according to claim 57, wherein X is trans--CH═CH--.
 59. A compound according to claim 58, wherein X is trans--CH═CH--.
 60. 4,5-didehydro-19-hydroxy-19-methyl-PGE₁, amide, a compound according to claim
 59. 61. 4,5-didehydro-19-hydroxy-19-methyl-15(S)-15-methyl-PGE₁, amide, a compound according to claim
 59. 62. A compound according to claim 58, wherein X is --C.tbd.C--.
 63. 4,5,13,14-tetradehydro-19-hydroxy-19-methyl-PGE₁, amide, a compound according to claim
 62. 64. 4,5,13,14-tetradehydro-19-hydroxy-19-methyl-16,16-difluoro-PGE₁, amide, a compound according to claim
 62. 65. A compound according to claim 57, wherein R₂ is hydroxymethyl.
 66. A compound according to claim 65, wherein X is trans--CH═CH--.
 67. 4,5-didehydro-19-hydroxy-19-methyl-11-deoxy-11α-hydroxymethyl-PGE₁, amide, a compound according to claim
 66. 68. 4,5-didehydro-19-hydroxy-19-methyl-11-deoxy-11.alpha.-hydroxymethyl-15(S)-15-methyl-PGE₁, amide, a compound according to claim
 66. 69. A compound according to claim 65, wherein X is --C.tbd.C--.
 70. 4,5,13,14-tetradehydro-19-hydroxy-19-methyl-11-deoxy-11.alpha.-hydroxymethyl-PGE₁, amide, a compound according to claim
 69. 71. 4,5,13,14-tetradehydro-19-hydroxy-19-methyl-11-deoxy-11α-hydroxymethyl-16,16-difluoro-PGE₁, amide, a compound according to claim
 69. 72. A compound according to claim 26, wherein W is methylene.
 73. A compound according to claim 72, wherein R₂ is hydroxyl.
 74. A compound according to claim 73, wherein X is trans--CH═CH--.
 75. 4,5-didehydro-19-hydroxy-19-methyl-9-deoxo-9-methylene-PGE₁, amide, a compound according to claim
 74. 76. 4,5-didehydro-19-hydroxy-19-methyl-9-deoxo-9-methylene-15(S)-15-methyl-PGE₁, amide, a compound according to claim
 74. 77. A compound according to claim 73, wherein X is --C.tbd.C--.
 78. 4,5,13,14-tetradehydro-19-hydroxy-19-methyl-9-deoxo-9-methylene-PGE₁, amide, a compound according to claim
 77. 79. 4,5,13,14-tetradehydro-19-hydroxy-19-methyl-9-deoxo-9-methylene-16,16-difluoro-PGE₁, amide, a compound according to claim
 77. 80. A compound according to claim 72, wherein R₂ is hydroxymethyl.
 81. A compound according to claim 80, wherein X is trans--CH═CH--.
 82. 4,5-didehydro-19-hydroxy-19-methyl-9-deoxo-9-methylene-11-deoxy-11α-hydroxymethyl-PGE₁, amide, a compound according to claim
 81. 83. 4,5-didehydro-19-hydroxy-19-methyl-9-deoxo-9-methylene-11-deoxy-11.alpha.-hydroxymethyl-15(S)-15-methyl-PGE₁, amide, a compound according to claim
 81. 84. A compound according to claim 80, wherein X is --C.tbd.C--.
 85. 4,5,13,14-tetradehydro-19-hydroxy-19-methyl-9-deoxo-9-methylene-11-deoxy-11α-hydroxymethyl-PGE₁, amide, a compound according to claim
 84. 86. 4,5,13,14-tetradehydro-19-hydroxy-19-methyl-9-deoxo-9-methylene-11-deoxy-11α-hydroxymethyl-16,16-difluoro-PGE₁, amide, a compound according to claim
 84. 87. A compound according to claim 1, wherein D is trans--(CH₂)₃ --CH═CH--.
 88. A compound according to claim 87, wherein W is α-OH:β-H.
 89. A compound according to claim 88, wherein R₂ is hydroxyl and X is trans--CH═CH--.
 90. 2,3-didehydro-19-hydroxy-19-methyl-PGF₁ α, amide, a compound according to claim
 89. 91. 2,3-didehydro-19-hydroxy-19-methyl-16,16-difluoro-PGF₁ α, amide, a compound according to claim
 89. 92. 2,3-didehydro-19-hydroxy-19-methyl-15(S)-15-methyl-PGF₁ α, amide, a compound according to claim
 89. 93. A compound according to claim 88, wherein R₂ is hydroxymethyl and X is trans--CH═CH--.
 94. 2,3-didehydro-19-hydroxy-19-methyl-11-deoxy-11α-hydroxymethyl-PGF₁ α, amide, a compound according to claim
 93. 95. 2,3-didehydro-19-hydroxy-19-methyl-11-deoxy-11α-hydroxymethyl-16,16-difluoro-PGF₁ α, amide, a compound according to claim
 93. 96. 2,3-didehydro-19-hydroxy-19-methyl-11-deoxy-11α-hydroxymethyl-15(S)-15-methyl-PGF₁ α, amide, a compound according to claim
 93. 97. A compound according to claim 87, wherein W is β-OH:α-H.
 98. A compound according to claim 97, wherein R₂ is hydroxyl and X is trans--CH═CH--.
 99. 2,3-didehydro-19-hydroxy-19-methyl-PGF₁ β, amide, a compound according to claim
 98. 100. 2,3-didehydro-19-hydroxy-19-methyl-16,16-difluoro-PGF₁ β, amide, a compound according to claim
 98. 101. 2,3-didehydro-19-hydroxy-19-methyl-15(S)-15-methyl-PGF₁ β, amide, a compound according to claim
 98. 102. A compound according to claim 97, wherein R₂ is hydroxymethyl and X is trans--CH--CH--.
 103. 2,3-didehydro-19-hydroxy-19-methyl-11-deoxy-11.sub.α -hydroxymethyl-PGF₁ β, amide, a compound according to claim
 102. 104. 2,3-didehydro-19-hydroxy-19-methyl-11-deoxy-11α-hydroxymethyl-16,16-difluoro-PGF₁ β, amide, a compound according to claim
 102. 105. 2,3-didehydro-19-hydroxy-19-methyl-11-deoxy-11α-hydroxymethyl-15(S)-15-methyl-PGF₁ β, amide, a compound according to claim
 102. 106. A compound according to claim 87, wherein W is oxo.
 107. A compound according to claim 106, wherein R₂ is hydroxyl and X is trans--CH═H--.
 108. 2,3-didehydro-19-hydroxy-19-methyl-PGE₁, amide, a compound according to claim
 107. 109. 2,3-didehydro-19-hydroxy-19-methyl-16,16-difluoro-PGE₁, amide, a compound according to claim
 107. 110. 2,3-didehydro-19-hydroxy-19-methyl-15(S)-15-methyl-PGE₁, amide, a compound according to claim
 107. 111. A compound according to claim 106, wherein R₂ is hydroxymethyl and X is trans--CH═CH--.
 112. 2,3-didehydro-19-hydroxy-19-methyl-11-deoxy-11α-hydroxymethyl-PGE₁, amide, a compound according to claim
 111. 113. 2,3-didehydro-19-hydroxy-19-methyl-11-deoxy-11α-hydroxymethyl-16,16-difluoro-PGE₁, amide, a compound according to claim
 111. 114. 2,3-didehydro-19-hydroxy-19-methyl-11-deoxy-11α-hydroxymethyl-15(S)-15-methyl-PGE₁, amide, a compound according to claim
 111. 115. A compound according to claim 57, wherein W is methylene.
 116. A compound according to claim 115, wherein R₂ is hydroxyl and X is trans--CH═CH--.
 117. 2,3-didehydro-19-hydroxy-19-methyl-9-deoxo-9-methylene-PGE₁, amide, a compound according to claim
 116. 118. 2,3-didehydro-19-hydroxy-19-methyl-9-deoxo-9-methylene-16,16-difluoro-PGE₁, amide, a compound according to claim
 116. 119. 2,3-didehydro-19-hydroxy-19-methyl-9-deoxo-9-methylene-15(S)-15-methyl-PGE₁, amide, a compound according to claim
 116. 120. A compound according to claim 115, wherein R₂ is hydroxymethyl and X is trans--CH═CH--.
 121. 2,3-didehydro-19-hydroxy-19-methyl-9-deoxo-9-methylene-11-deoxy-11α-hydroxymethyl-PGE₁, amide, a compound according to claim
 120. 122. 2,3-didehydro-19-hydroxy-19-methyl-9-deoxo-9-methylene-11-deoxy-11α-hydroxymethyl-16,16-difluoro-PGE₁, amide, a compound according to claim
 120. 123. 2,3-didehydro-19-hydroxy-19-methyl-9-deoxo-9-methylene-11-deoxy-11α-hydroxymethyl-15(S)-15-methyl-PGE₁, amide, a compound according to claim
 120. 124. A compound according to claim 2, wherein D is --(CH₂)₃ --(CH₂)_(g) --CH₂ --, wherein g is zero, one, two, or three.
 125. A compound according to claim 124, wherein g is one.
 126. A compound according to claim 125, wherein W is α-OH:β-H.
 127. A compound according to claim 126, wherein R₂ is hydroxyl.
 128. A compound according to claim 127, wherein X is trans--CH═CH--.
 129. 19-hydroxy-19-methyl-PGF₁ α, amide, a compound according to claim
 128. 130. 16,16-dimethyl-19-hydroxy-19-methyl-PGF₁ α, amide, a compound according to claim 128,.
 131. 16,16-difluoro-19-hydroxy-19-methyl-PGF₁ α, amide, a compound according to claim
 128. 132. A compound according to claim 127, wherein X is --CH₂ CH₂ --.
 133. 13,14-dihydro-19-hydroxy-19-methyl-PGF₁ α, amide, a compound according to claim
 132. 134. A compound according to claim 126, wherein R₂ is hydroxymethyl.
 135. A compound according to claim 134, wherein X is trans--CH═CH--.
 136. 11-deoxy-11α-hydroxymethyl-19-hydroxy-19-methyl-PGF₁ α, amide, a compound according to claim
 135. 137. 11-deoxy-11α-hydroxymethyl-16,16-dimethyl-19-hydroxy-19-methyl-PGF₁ α, amide, a compound according to claim
 135. 138. 11-deoxy-11α-hydroxymethyl-16,16-difluoro-19-hydroxy-19-methyl-PGF₁ α, amide, a compound according to claim
 135. 139. A compound according to claim 134, wherein X is --CH₂ CH₂ --.
 140. 11-deoxy-11α-hydroxymethyl-13,14-dihydro-19-hydroxy-19-methyl-PGF₁ α, amide, a compound according to claim
 139. 141. A compound according to claim 125, wherein W is β-OH:α-H.
 142. A compound according to claim 141, wherein R₂ is hydroxyl.
 143. A compound according to claim 142, wherein X is trans--CH═CH--.
 144. 19-hydroxy-19-methyl-PGF₁ β, amide, a compound according to claim
 143. 145. 16,16-dimethyl-19-hydroxy-19-methyl-PGF₁ β, amide, a compound according to claim
 143. 146. 16,16-difluoro-19-hydroxyl-19-methyl-PGF₁ β, amide, a compound according to claim
 143. 147. A compound according to claim 142, whrein X is --CH₂ CH₂ --.
 148. 13,14-dihydro-19-hydroxy-19-methyl-PGF₂ β, amide, a compound according to claim
 147. 149. A compound according to claim 125, wherein W is oxo.
 150. A compound according to claim 149, wherein R₂ is hydroxyl.
 151. A compound according to claim 150, wherein X is trans--CH═CH--.
 152. 19-hydroxy-19-methyl-PGE₁, amide, a compound according to claim
 151. 153. 16,16-dimethyl-19-hydroxy-19-methyl-PGE₁, amide, a compound according to claim
 151. 154. 16,16,difluoro-19-hydroxy-19-methyl-PGE₁, amide, a compound according to claim
 151. 155. A compound according to claim 150, wherein X is --CH₂ CH₂ --.
 156. 13,14-dihydro-19-hydroxy-19-methyl-PGE₁, amide, a compound according to claim
 155. 157. A compound according to claim 149, wherein R₂ is hydroxymethyl.
 158. A compound according to claim 157, wherein X is trans--CH═CH--.
 159. 11-deoxy-11α-hydroxymethyl-19-hydroxy-19-methyl-PGE₁, amide, a compound according to claim
 158. 160. 11-deoxy-11α-hydroxymethyl-16,16-dimethyl-19-hydroxy-19-methyl-PGE₁, amide, a compound according to claim
 158. 161. 11-deoxy-11α-hydroxymethyl-16,16-difluoro-19-hydroxy-19-methyl-PGE₁, amide, a compound according to claim
 158. 162. A compound according to claim 157, wherein X is --CH₂ CH₂ --.
 163. 11-deoxy-11α-hydroxymethyl-13,14-dihydro-19-hydroxy-PGE₁, amide, a compound according to claim
 162. 164. A compound according to claim 125, wherein W is methylene.
 165. A compound according to claim 164, wherein R₂ is hydroxyl.
 166. A compound according to claim 165, wherein X is trans--CH═CH--.
 167. 9-deoxo-9-methylene-19-hydroxy-19-methyl-PGE₁, amide, a compound according to claim
 166. 168. 9-deoxo-9-methylene-16,16-dimethyl-19-hydroxy-19-methyl-PGE₁, amide, a compound according to claim
 166. 169. 9-deoxo-9-methylene-16,16-difluoro-19-hydroxy-19-methyl-PGE₁, amide, a compound according to claim
 167. 170. A compound according to claim 165, wherein X is --CH₂ CH₂ --.
 171. 9-deoxo-9-methylene-13,14-dihydro-19-hydroxy-19-methyl-PGE₁, amide, a compound according to claim
 170. 172. A compound according to claim 164, wherein R₂ is hydroxymethyl.
 173. A compound according to claim 172, wherein X is trans--CH═CH--.
 174. 9-deoxo-9-methylene-11-deoxy-11α-hydroxymethyl-19-hydroxy-19-methyl-PGE₁, amide, a compound according to claim
 173. 175. 9-deoxo-9-methylene-11-deoxy-11α-hydroxymethyl-16,16-dimethyl-19-hydroxy-19-methyl-PGE₁, amide, a compound according to claim
 173. 176. 9-deoxo-9-methylene-11-deoxy-11α-hydroxymethyl-16,16-difluoro-19-hydroxy-19-methyl-PGE.sub.1, amide, a compound according to claim
 173. 177. A compound according to claim 172, wherein X is --CH₂ CH₂ --.
 178. 9-deoxo-9-methylene-11-deoxy-11α-hydroxymethyl-13,14-dihydro-19-hydroxy-19-methyl-PGE₁, amide, a compound according to claim
 177. 